Clinical Trials Register

Summary
EudraCT Number:	2007-005994-79
Sponsor's Protocol Code Number:	3133K1-3000-WW
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2008-04-23
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-005994-79

A.3

Full title of the trial

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Trial of Bapineuzumab (AAB-001, ELN115727) in Subjects With Mild to Moderate Alzheimer Disease Who Are Apolipoprotein E ε4 Non-Carriers

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

3133K1-3000-WW

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Wyeth Research Division of Wyeth Pharmaceuticals Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AAB-001
D.3.2	Product code	AAB-001
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bapineuzumab
D.3.9.2	Current sponsor code	AAB-001, WAY 203740 (ELN115727)
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	anticorpo monoclonale umanizzato anti-Abeta peptide IgG1

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Alzheimer Disease

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10012271
E.1.2	Term	Dementia Alzheimer's type

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the efficacy of multiple doses of intravenously (IV) administered bapineuzumab compared with placebo in subjects with mild to moderate AD as measured by both of the following: The change from baseline scores for the ADAS-Cog to week 78. The change from baseline scores for the DAD to week 78. The safety objective of this study is to assess the safety of multiple doses of IV administered bapineuzumab in subjects with mild to moderate AD versus placebo, including The incidence and severity of treatment-emergent adverse events (TEAEs). Clinically important changes in safety assessment results (including, as appropriate, vital signs, weight, clinical laboratory tests, immune complex and complement tests, ECGs, brain MRI scans, and physical and neurologic examinations).

E.2.2

Secondary objectives of the trial

To investigate the safety and efficacy of multiple doses of intravenously (IV) administered bapineuzumab compared with placebo in subjects with mild to moderate AD as measured in scores from baseline to week 78 in the NTB and CDR-SOB (key secondary mesures). Safety objective include the incidence and severity of treatment-emergent adverse events (TEAEs) and clinically important changes in safety assessment results.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

ALTRI SOTTOSTUDI: Sottostudi Facoltativi: -Immagine volumetrica alla Risonanza Magnetica - liquido cefalorachidiano - Sottostudi della tomografia ad emissione di positroni:amyloid-PET ed FDG-PE

E.3

Principal inclusion criteria

1.Signed and dated written informed consent obtained from the subject or the subject’s legally acceptable representative (if applicable) in accordance with the local regulations. The subject’s caregiver must also consent to participate in the study. 2.Man or surgically sterile or postmenopausal woman, aged ≥50 to <89 years. 3.Diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria. 4. MMSE score of 16 to 26, inclusive. 5. Rosen Modified Hachinski Ischemic Score ≤4. 6. Lives at home with appropriate caregiver capable of accompanying the subject on all clinic visits, or community dwelling with caregiver capable of accompanying the subject on all clinic visits and visiting with the subject approximately 5 times per week for the duration of the study. 7. Screening visit brain MRI scan consistent with the diagnosis of AD. 8. Fluency in local language and evidence of adequate premorbid intellectual functioning. 9. Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments. 10. Receiving stable doses of medication(s) for the treatment of nonexcluded medical condition(s) for at least 30 days prior to screening, and, if treated with cholinesterase inhibitors and/or memantine, all of the following conditions are also met: a. The subject is maintained on a stable dose regimen for at least 120 days prior to screening. b. The subject is free of any clinically important side effects attributable to the drug. c. The subject and caregiver agree that, barring unforeseen circumstances, they will continue the same regimen for the duration of the trial. 11. The subject and caregiver are likely to be able to participate in all scheduled evaluations and complete all required tests. 12. Willing to undergo apolipoprotein E (ApoE) genotype testing. 13. Noncarrier of ApoE4 according to genotyping at screening (ie, has zero copies of ApoE4). 14. In the opinion of the investigator, the subject and caregiver will be compliant and have a high probability of completing the study.

E.4

Principal exclusion criteria

1. Significant neurologic disease, other than AD, that may affect cognition.
2. Screening visit brain MRI scan indicative of any other significant abnormality, including but not limited to multiple microhemorrhages, evidence of a single prior hemorrhage >1 cm3, multiple lacunar infarcts or evidence of a single prior infarct >1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or space-occupying lesions (eg, arachnoid cysts or brain tumors, such as meningioma).
3. Current presence of a clinically important major psychiatric disorder (eg, major depressive disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) or symptom (eg, hallucinations) that could affect the subject’s ability to complete the study.
4. Current clinically important systemic illness that is likely to result in deterioration of the subject’s condition or affect the subject’s safety during the study.
5. History of clinically evident stroke or history of clinically important carotid or vertebrobasilar stenosis or plaque.
6. History of seizures, excluding febrile seizures in childhood.
7. Weight greater than 120 kg (264 lb).
8. History or evidence of any clinically important autoimmune disease or disorder of the immune system
(eg, Crohn disease, rheumatoid arthritis).
9. Clinically important infection within the last 30 days (eg, chronic persistent or acute infection, such as bronchitis or urinary tract infection [UTI]).
10. Treatment with immunosuppressive medications (eg, systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years.
11. Myocardial infarction within the last 2 years.
12. History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma, and squamous cell carcinoma of the skin.
13. Uncontrolled hypertension within 6 months prior to screening.
14. Other clinically important abnormality on vital signs, physical examination, neurologic examination, laboratory results, or electrocardiogram (ECG) examination (eg, atrial fibrillation) that could compromise the study or be detrimental to the subject.
15. Hemoglobin level less than 11 g/dL.
16. Blood donation (routine blood donation) in the 90 days prior to screening.
17. Excessive smoking, defined as more than 20 cigarettes per day.
18. History of alcohol or drug dependence or abuse as defined by DSM-IV-TR criteria within the last 2 years.
19. Current use of anticonvulsant agent for seizures, antiparkinson agents, or anticoagulant medications (except the use of aspirin 325 mg/day or less), or regular use (>2 times per week during the 4 weeks preceding screening) of opioid pain relievers (and related synthetic derivatives).
20. Current use of prescription or nonprescription medication for cognitive enhancement (eg, ginkgo biloba or huperzine) other than cholinesterase inhibitors and memantine as previously described.
21. Discontinuation of cholinesterase inhibitors, memantine, cognitive-enhancing agents (eg, ginkgo biloba or huperzine), or drugs that potentially affect cognition in the 60 days prior to screening.
22.Unless the subject is maintained on a stable dose regimen for at least 30 days prior to screening, use of any other medications with the potential to affect cognition other than cholinesterase inhibitors or memantine (including, but not limited to, anxiolytics, sedatives, hypnotics, antipsychotics, herbal agents, antidepressants, over-the-counter (OTC) sleeping aids, sedating antiallergy medications, vitamin E, thyroid supplements, and vitamin B12 supplements by injection).

E.5 End points

E.5.1

Primary end point(s)

ADAS-Cog and DAD

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Same IMP used at different dosage (0,5; 1,0 e 2,0 mg/kg)

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

132

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last Patient Last Visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

malati di Alzheimer possono aver necessita' dirappresentante accettabile dal punto di vista legale

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

110

F.4.2

For a multinational trial

F.4.2.1

In the EEA

900

F.4.2.2

In the whole clinical trial

1250

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

I soggetti, dopo la partecipazione allo studio,potranno continuare o iniziare terapie in commercio per la propria patologia. Un possibile protocollo di estensione del presente studio e' in fase di valutazione.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2008-04-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-03-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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